人羊膜间充质干细胞对大鼠胶原性关节炎的疗效及免疫调节作用  

Therapeutic effects and immunologic regulation of human amniotic mesenchymal stem cells on rats with collagen-induced arthritis

作　　者：肖瑶[1] 方宁[1] 陈代雄[1] 余丽梅[1] 章涛[1] 赵春华[2] 

机构地区：[1]遵义医学院附属医院贵州省细胞工程重点实验室,563003 [2]中国医学科学院基础医学研究所组织工程中心,北京10005

出　　处：《免疫学杂志》2013年第6期461-466,共6页Immunological Journal

基　　金：国家科技重大专项课题(2009ZX09503-025);贵州省科技计划发展项目([2009]3017;2051)

摘　　要：目的探讨人羊膜间充质干细胞(hAMSCs)对大鼠胶原性性关节炎(CIA)的疗效和免疫调节作用。方法从人羊膜分离培养hAMSCs,流式细胞术(FCM)分析其表型;用牛Ⅱ型胶原和弗氏佐剂诱导大鼠CIA模型;动物随机分为正常对照组、CIA模型组、hAMSCs治疗组、培养基对照组和氨甲蝶呤(MTX)治疗组,每组6只。hAMSCs治疗组经双踝关节腔注射2×106hAMSCs。观察关节炎指数(AI)、足趾容积、关节影像和病理变化以评价疗效;流式细胞术(FCM)检测外周血单个核细胞中淋巴细胞亚群百分比。结果与模型组和培养基组比较,hAMSCs治疗组和MTX治疗组AI和足趾容积均明显下降(P<0.05),踝关节关节骨质破坏和炎症反应减轻;Th1、Th2、Th17、CTL1、CTL2和NKT亚群百分比明显下降,而Foxp3+Treg细胞显著上调(P<0.01)。hAMSCs治疗组和MTX治疗组比较,淋巴细胞亚群的变化相似,但后者Foxp3+Treg细胞上调幅度不及前者(P<0.01)。结论 hAMSCs可能通过调节Foxp3+Treg和Th17细胞发挥对大鼠CIA的治疗作用。This study aimed to investigate the therapeutic action and immunoregulatory effect of human amniotic mesenchymal stem cells （hAMSCs） on rats with collagen-induced arthritis （CIA）. The hAMSCs wereisolated from human amnion and cultured in vitro, then phenotype was analyzed by flow cytometry （FCM）; CIA was induced in Wistar rats with bovine type Ⅱ collagen and Freund＇s adjuvant. Rats were randomly divided into 5groups： normal controls, untreated models, hAMSCs treated models, medium treated models, and methotrexate （MTX） treated models, hAMSCs were injected intra-articularly into ankle joints of the rats with CIA. Therapeuticeffect of hAMSCs on CIA was assessed through arthritis index （AI） score, joint volume, X-ray and pathological examination of target joints. Frequency of lymphocyte subsets in peripheral blood mononuclear cells （PBMCs） wereobserved by FCM. We found that compared with untreated model and medium treated model, hAMSCs treated model demonstrated lower AI and decreased volume of target joints （P〈0.05）, alleviated pathological damage of target joints,decreased percentage of Th1, Th2, Thl7, CTL1, CTL2 and NKT （P〈0.01）, but higher Foxp3＋ Treg level （P〈 0.01）. We concluded that hAMSCs may inhibit the development of CIA through regulating the Foxp3＋Treg and Thl7 cells.

关 键 词：人羊膜间充质干细胞 胶原性关节炎 免疫调节 大鼠 

分 类 号：R684.3[医药卫生—骨科学]